Effects of picrotoxin, naloxone, and vagotomy on chlordiazepoxide-induced respiratory depression. 1979

M Billingsley, and A Suria, and J Williams

Intravenous administration of chlordiazepoxide (CDP) caused respiratory depression in both rats and cats. The maximally tolerated dose of CDP was found to be 165 +/- 15 mg/kg, i.v., in rats. Pretreatment with picrotoxin (1.5 mg/kg) or naloxone (20 mg/kg, i.v.) significantly increased the maximally tolerated dose of CDP to 330 +/- 40 mg/kg, i.v., and 270 +/- 35 mg/kg, i.v., respectively. The protective effects of both naloxone and picrotoxin were absent in bilaterally vagotomized rats. Naloxone pretreatment (25 mg/kg, i.v.) was also found to block the respiratory depressant effects of CDP in anesthetized cats, but had no effect on the cardiovascular actions of CDP. It is possible that the respiratory effects of CDP are due to its actions on GABA receptors, and that peripheral GABA receptors may mediate the protective actions of picrotoxin and naloxone.

UI MeSH Term Description Entries
D009270 Naloxone A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. MRZ 2593-Br,MRZ-2593,Nalone,Naloxon Curamed,Naloxon-Ratiopharm,Naloxone Abello,Naloxone Hydrobromide,Naloxone Hydrochloride,Naloxone Hydrochloride Dihydride,Naloxone Hydrochloride, (5 beta,9 alpha,13 alpha,14 alpha)-Isomer,Naloxone, (5 beta,9 alpha,13 alpha,14 alpha)-Isomer,Narcan,Narcanti,Abello, Naloxone,Curamed, Naloxon,Dihydride, Naloxone Hydrochloride,Hydrobromide, Naloxone,Hydrochloride Dihydride, Naloxone,Hydrochloride, Naloxone,MRZ 2593,MRZ 2593 Br,MRZ 2593Br,MRZ2593,Naloxon Ratiopharm
D010852 Picrotoxin A mixture of PICROTOXININ and PICROTIN that is a noncompetitive antagonist at GABA-A receptors acting as a convulsant. Picrotoxin blocks the GAMMA-AMINOBUTYRIC ACID-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates. 3,6-Methano-8H-1,5,7-trioxacyclopenta(ij)cycloprop(a)azulene-4,8(3H)-dione, hexahydro-2a-hydroxy-9-(1-hydroxy-1-methylethyl)-8b-methyl-, (1aR-(1aalpha,2abeta,3beta,6beta,6abeta,8aS*,8bbeta,9S*))-, compd. with (1aR-(1aalpha,2abeta,3beta,6beta,6abeta,8,Cocculin
D012119 Respiration The act of breathing with the LUNGS, consisting of INHALATION, or the taking into the lungs of the ambient air, and of EXHALATION, or the expelling of the modified air which contains more CARBON DIOXIDE than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration ( Breathing
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002415 Cats The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801) Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D002707 Chlordiazepoxide An anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawal. Methaminodiazepoxide,7-Chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine-4-oxide,7-Chloro-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-amine 4-oxide,Chlordiazepoxide Hydrobromide,Chlordiazepoxide Hydrochloride,Chlordiazepoxide Monohydrochloride,Chlordiazepoxide Perchlorate,Chlozepid,Elenium,Librium,7 Chloro 2 methylamino 5 phenyl 3H 1,4 benzodiazepine 4 oxide,7 Chloro N methyl 5 phenyl 3H 1,4 benzodiazepin 2 amine 4 oxide,Hydrobromide, Chlordiazepoxide,Hydrochloride, Chlordiazepoxide,Monohydrochloride, Chlordiazepoxide,Perchlorate, Chlordiazepoxide
D003864 Depression, Chemical The decrease in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical. Chemical Depression,Chemical Depressions,Depressions, Chemical
D005260 Female Females
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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